These studies are designed to elucidate mechanisms associated with the proliferation and differentiation of normal red and white blood cell precursors in both experimental animals and man. Parallel studies will be performed with acute leukemia and erythroleukemia cells to provide understanding of the abnormalities underlying malignancies of the hemopoietic system. In studies of erythropoiesis attention will be given to the developmental patterns and responses to erythropoietin of hemoglobin synthesis, plasma membrane proteins and iron transport by transferrin membrane receptors. Other experiments will be concerned with the significance of erythroid precursor cells, CFU-E, and BFU-E, in normal and pathologic erythropoiesis. Studies will be performed with cells from normal mice, mice with Friend virus-induced erythroleukemia, and cultured erythroleukemia cells before and after chemical induction of differentiation. Studies will also be done with cells from normal human subjects and patients with hematological disorders such as erythroleukemia and sideroblastic anemia. Factors which regulate normal granulocytopoiesis will be investigated with techniques of cell culture, including the diffusion chamber method and colony assays of hemopoietic precursor cells, with attention to alterations in stem cell proliferation, microenvironmental influences and cell-cell interactions. Similar methods will be used to investigate the proliferation of leukemic cells and the suppression of normal cell growth by co-cultured acute leukemic cells. These studies will be performed with cells from both mice and human subjects. Additional studies will be concerned with the pathogenesis of other clinical disorders affecting granulocytes such as drug-induced agranulocytosis.